Major Histocompatibility Complex MHC History Inbred mouse strains

主要组织相容性复合体 Major Histocompatibility Complex MHC 肖健

History Inbred mouse strains近交系 - all genes are identical 不同品系小鼠的皮肤移植表明排斥或接纳均受遗传控制 接纳 Skin from an inbred mouse grafted onto the same strain of mouse 排斥 Skin from an inbred mouse grafted onto a different strain of mouse

Hyperacute rejection of a renal allograft. Kidney is deep red and swollen.

Terms of some species animals Types of graft Species mice human rabit monkey pig term H-2 HLA SLA DLA RHLA dog chook B

Map of the Human MHC from the Human Genome Project 3, 838, 986 bp 224 genes on chromosome 6 The MHC sequencing consortium Nature 401, 1999 224个基因座位中，128个为功能性基因，96个为假基因

HLA的结构 HLA centromere DP DN DO DQ DR C 4, C 2, Bf TNF HLA-DP HLA-DQ HLA-DR C 4, C 2, Bf Ag Ag Ag TNF HLA-ⅡAg B HLA-B + β 2 m HLA-Ⅲ product C E HLA-C + β 2 m A HLA-A + β 2 m HLA-I Ag G

HLA I 类基因区 Class II DP DQ DR Class III Class I C 4 B C 4 A B 1 C 2 HSP TNF B C E A H MIC G F HLA II 类基因区 Class II RING DP B 2 A 2 B 1 A 1 DM A B LMP 2 LMP 7 TAP 1 DQ TAP 2 B 2 A 2 B 3 B 1 A 1 DR B* A a 1 b 1 a 2 b 2 a 1 a 3 b 2 m

MHC I 类基因的多态性 N. o. of polymorphisms 2798 Class I 2132 1672 A B C 11 2 50 E F G a 2 a 1 a 3 b 2 m

MHC II 类基因的多态性 No of polymorphism s 1196 Class II 668 alleles (492 in July 2000) 179 58 7 A B 1 DR B 3 36 49 A 1 158 B 1 DQ A 1 B 1 DP 4 6 8 8 A B DM DO a 1 b 1 a 2 b 2 *基于共显性表达的特点，因而每个个体 通常拥有的经典I 通常拥有的经典 类和 II 类HLA等位基因产 物有12种

Haplotype (单体型) HLA complex is a group of closely linked genes. a group of HLA genes on a single chromosome is called haplotype. 单位型是指一条染色 体上MHC不同座位等位基因因紧密连锁而形成的特定组合。 A 1 A 2 haplotype: A 1、B 8 / A 2、B 35 B 8 B 35

diploid （二倍体） Father Mother A 1 A 2 B 8 B 35 a 1 × b A 2 A 10 B 40 B 16 c 2 d 3 4 A 1 A 10 A 2 A 2 B 8 B 16 B 40 B 35 a d b d c b c a

MHC 分子 MHC分子的基本结构 MHC-I MHC- II 2 1 1 1 3 2 m 2 2 Peptide-binding region immunoglobulin-like region Transmembrane region

MHC 分子的分布 Tissue MHC class I T cells B cells Macrophages Other APC +++ +++ +/+++ +++ Thymus epithelium Neutrophils Hepatocytes Kidney Brain Erythrocytes +++ + - MHC class II -

MHC分子结构小结 a-chain Peptide b 2 -M MHC class I accommodate peptides of 8 -10 amino acids Peptide b-chain MHC class II accommodate peptides of >13 amino acids

MHC 的生物学功能 处理与提呈蛋白质抗原 Endogenous antigen presentation pathway Exogenous antigen presentation pathway Types of graft

MHC-I molecule presentation of antigen cellular nuclear CD 8+ T cell TCR CD 28 MHC-I B 7 Antigenic peptide APC Transfer t the surface of the cell 4 endogenic protein 3 assembling MHC-I, ß 2 m antigenic peptide synthesis of MHC－I and proteasome 2 1 peptides TAP

MHC-II molecule presentation of antigen 细 胞 核 CD 4+ T cell CD 4 TCR CD 28 Antigenic peptide APC Transfer to the surface of cell B 7 5 2 4 Transfer , chains phagosome 3 lysosome 1 Synthesis of MHC-II molecule

Table 3. Examples of significant HLA and disease associations Frequency in Associated Alleles Patients 强直性脊柱炎 Ankylosing spondylitis B 27 90 9 87. 4 Reiter's disease (syndrome) B 27 79 9 37. 0 急性眼色素层炎 Acute anterior uveitis B 27 52 9 10. 4 牛皮癣 Psoriasis vulgaris Cw 6 87 33 13. 3 DR 3 85 26 15. 4 DR 3 79 26 10. 8 DR 3/4 91 57 25. 0 Disease 疱疹性皮炎 Dermatitis herpetiformis 乳糜泻 Celiac Disease 胰岛素依赖性糖尿病 Insulin-dependent diabetes mellitus Control Relative Risk

强直性脊柱炎 ankylosing spondylitis (B 27),

Psoriasis牛皮癣 of the hand (Cw 6 )

Psoriasis牛皮癣

Dermatitis Herpetiformis疱疹性皮炎: Mouth Mucosa (DR 3)

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